We plan to investigate the mechanisms of hyperthyroidism in Graves' disease with particular attention to possible immunopathogenesis. We will study human thyroid tissue in the form of isolated cells, membranes, membrane fragments, reaggregated cells and tissue slices. The early steps of thyroid secretion which include binding of the thyroid stimulator and ingestion of colloid have some similarity to the processes of opsonification and phagocytosis by macrophages. Therefore, methods helpful in studying phagocytosis will be emphasized. Several thyroid stimulators including LATS, HTS (human thyroid stimulator) and the effects of immune lymphocytes will be studied. Lymphocyte subpopulations from patients with thyroid diseases will be cultured with stimulants in an effort to learn which lymphocyte population is responsible for the production of antibodies involved in the disease.